Monogenic Diabetes in Children and Adolescents: Recognition and Treatment Options

Sanyoura, May; Philipson, Louis H.; Naylor, Rochelle N.

doi:10.1007/s11892-018-1024-2

Cited by 81 publications

(57 citation statements)

References 125 publications

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“…Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes, a clinically and genetically heterogeneous group of endocrine disorders resulting from mutations affecting a single gene involved in pancreatic beta cell function [ 1 ]. In 1975, Fajans and Tattersall used the acronym MODY for the first time in the literature to describe a cohort of patients with familial diabetes characterized by autosomal dominant inheritance of a primary defect in insulin secretion [ 2 – 4 ].…”

Section: Introductionmentioning

confidence: 99%

The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY)

Nkonge

2020

Clin Diabetes Endocrinol

115

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Background The most common type of monogenic diabetes is maturity-onset diabetes of the young (MODY), a clinically and genetically heterogeneous group of endocrine disorders that affect 1–5% of all patients with diabetes mellitus. MODY is characterized by autosomal dominant inheritance but de novo mutations have been reported. Clinical features of MODY include young-onset hyperglycemia, evidence of residual pancreatic function, and lack of beta cell autoimmunity or insulin resistance. Glucose-lowering medications are the main treatment options for MODY. The growing recognition of the clinical and public health significance of MODY by clinicians, researchers, and governments may lead to improved screening and diagnostic practices. Consequently, this review article aims to discuss the epidemiology, pathogenesis, diagnosis, and treatment of MODY based on relevant literature published from 1975 to 2020. Main body The estimated prevalence of MODY from European cohorts is 1 per 10,000 in adults and 1 per 23,000 in children. Since little is known about the prevalence of MODY in African, Asian, South American, and Middle Eastern populations, further research in non-European cohorts is needed to help elucidate MODY’s exact prevalence. Currently, 14 distinct subtypes of MODY can be diagnosed through clinical assessment and genetic analysis. Various genetic mutations and disease mechanisms contribute to the pathogenesis of MODY. Management of MODY is subtype-specific and includes diet, oral antidiabetic drugs, or insulin. Conclusions Incidence and prevalence estimates for MODY are derived from epidemiologic studies of young people with diabetes who live in Europe, Australia, and North America. Mechanisms involved in the pathogenesis of MODY include defective transcriptional regulation, abnormal metabolic enzymes, protein misfolding, dysfunctional ion channels, or impaired signal transduction. Clinicians should understand the epidemiology and pathogenesis of MODY because such knowledge is crucial for accurate diagnosis, individualized patient management, and screening of family members.

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Section: Introductionmentioning

confidence: 99%

The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY)

Nkonge

2020

Clin Diabetes Endocrinol

115

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“…The final diagnosis is established on the basis of the result of a genetic test [9]. The importance of diagnosing monogenic diabetes results from the possibility of family prognosis [10]. The most common forms of monogenic diabetes are Maturity Onset Diabetes of the Young (MODY), mitochondrial diabetes and neonatal diabetes [11].…”

Section: Monogenic Diabetesmentioning

confidence: 99%

Emergency medicine point of view on epidemiology of diabetes and diabetes-related complications

Szalast

Szarpak

2020

Disaster Emerg Med J

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INTRODUCTION: Despite centuries of research and clinical work, the diagnosis of diabetes was still treated as a quick death sentence at the beginning of the 20th century. Unfortunately, the number of patients with diabetes is increasing every year. Type 2 diabetes is increasingly common among young people: children and adolescents. The article discusses the type of diabetes and the importance of rapid diagnosis and management. Type 1 diabetes, type 2 diabetes, latent autoimmune diabetes in adults, monogenic diabetes, gestational diabetes were analysed. Life-threatening conditions resulting from complications of diabetes including diabetic ketoacidosis, hyperglycaemic-hyperosmolar state, hypoglycaemia, lactic acidosis were discussed, and the first-line emergency treatment were analysed. The life-threatening complications of diabetes and rescue procedures in these conditions were discussed in detail. CONCLUSIONS: Due to the frequency of life-threatening complications, diabetes is a heavy burden on the medical staff. Adequate diagnosis and implementation of appropriate treatment significantly improve the patient's condition.

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“…Insulin deficiency is usually attributed to the autoimmune destruction of islet β cells in childhood diabetes, but monogenic diabetes is also a common cause of insulin deficiency (4). The prevalence of obesity has increased rapidly and type 2 DM (T2DM) incidence in children has also been increasing.…”

Section: Introductionmentioning

confidence: 99%

Detection and analysis of glucose metabolism‑related genes in childhood diabetes using targeted next‑generation sequencing: In pediatric population‑a hospital‑based study

Wang

et al. 2020

Exp Ther Med

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The aim of the present study was to explore the genetic causes of antibody-negative diabetes and investigate its characteristics. A total of 64 patients with new-onset diabetes (>6 m, <16 y) were identified and their initial clinical characteristics were analyzed. Of which, 32 cases with autoantibody-negative diabetes (male, 16 cases; female, 16 cases) were screened for auto-antibodies, including islet cell antibody, glutamic acid decarboxylase antibody and islet antigen-2, which were negative, and fasting C-peptide was ≥0.3 ng/ml. Peripheral blood DNA was extracted from the subjects and their parents for high-throughput sequencing of glucose metabolism-related genes. The group with the pathogenic variation was used as the experimental group. The control group comprised 32 cases of type 1 diabetes (T1D). Their baseline clinical characteristics were determined and statistically analyzed. Out of the 32 antibody-negative diabetes cases, 21 had possible related mutations. There were 2 HNF1B missense mutations, 1 GCK missense mutation and 1 de novo KCNJ11 missense mutation. GCGR c.118G>A p.G40S was present in patients with type 2 DM (T2DM); the locus is associated with T2DM susceptibility in China. An LIPC frameshift mutation was identified, which had not been previously reported; the gene was found to markedly affect protein function and be associated with glucose and lipid metabolism. It was concluded that children with antibody-negative T1D have monogenic diabetes. The present findings shed light on the etiology and mechanism of antibody-negative diabetes, which will enable the comprehensive analysis of antibody-negative diabetes genotypes and phenotypes and further help improved precision treatment.

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Monogenic Diabetes in Children and Adolescents: Recognition and Treatment Options

Cited by 81 publications

References 125 publications

The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY)

The epidemiology, molecular pathogenesis, diagnosis, and treatment of maturity-onset diabetes of the young (MODY)

Emergency medicine point of view on epidemiology of diabetes and diabetes-related complications

Detection and analysis of glucose metabolism‑related genes in childhood diabetes using targeted next‑generation sequencing: In pediatric population‑a hospital‑based study

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